CTIM-04. PHASE I STUDY OF IBRUTINIB WITH RADIATION AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma is associated with dismal outcomes a survival of 15-18 months. A major challenge in glioblastoma the inability to effectively target glioma stem cells (GSCs) that have capacity for self-renewal. GSCs are resistant radiation and traditional chemotherapy agents. Ibrutinib first-in-class, potent, small-molecule tyrosine kinase inhibitor Bruton’s Tyrosine Kinase (BTK) Bone marrow X-linked (BMX). BMX nonreceptor activates STAT3 signaling maintain self-renewal tumorigenic potential GSCs. Hence combination ibrutinib temozolomide promising approach. METHODS Unmethylated MGMT GBM patients received daily 60 Gy over 6 weeks (Arm 1). methylated Temozolomide at 75 mg/m2 addition 2). Starting dose (level 1) was 420 mg daily, level 2 560 -1 280 mg. Patients adjuvant The primary endpoint included maximum tolerated (MTD) 1), ibrutinib, radiation, Progression-free overall secondary endpoints. RESULTS 27 (15 males, 12 females), median age 63 years (range, 34-77 years) were treated on two arms. Dose Limiting toxicity (DLT) Arm 1 grade 3 weakness, 4 transaminases, neutropenia. DLT rash, neutropenia, thrombocytopenia. too toxic 1, MTD confirmed 2. CONCLUSION radiation. Efficacy (PFS OS) will be presented.